Liver CirrhosesPhase 2/32018-001698-25NCT03780673
Efficacy of the Combination of Simvastatin Plus Rifaximin in Patients With Decompensated Cirrhosis to Prevent ACLF Development
A Phase 2/3 study testing Simvastatin and Rifaximin in people with Liver Cirrhoses, run by Judit Pich at 14 sites in 7 countries.
Trial summary
The aim of this study is to assess the efficacy of oral administration of simvastatin plus rifaximin in patients with decompensated cirrhosis to halt the progression of the disease as assessed by prevention of the development of ACLF Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Liver Cirrhoses
- What is being tested?
- Simvastatin and Rifaximin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 254 participants
- Where
- 14 sitesin 7 countries
- Study dates
- 3 Jan 2019to 1 Dec 2022
- Phase
- Phase 2/3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age ≥ 18 years old
- Cirrhosis defined by standard clinical criteria, ultrasonographic findings and/or histology
- Child-Pugh patients or Child-Pugh C patients (up to 12 points)
- Women of child-bearing potential must have a negative pregnancy test in serum before the inclusion in the study and agree to use highly effective contraceptive methods during the study. Highly effective contraceptive methods will include: intrauterine device, bilateral tubal occlusion, vasectomized partner and sexual abstinence.
Who cannot join
- Patients on treatment with statins or rifaximin up to one month before study inclusion.
- Patients with contraindications for statins or rifaximin therapy.
- Known hypersensitivity to simvastatin or rifaximin (or rifamycin derivatives).
- Patients with CK elevation of 50% or more above the upper limit of normal at study inclusion.
- Patients on treatment with potent inhibitors of CYP3A4 enzyme
- Patients on treatment with drugs with potential interactions with simvastatin
Show all 26Show fewer
- Patients with previous history of myopathy.
- Patients with previous history of intestinal obstruction or those who are at increased risk of this complication.
- Patients with ACLF according to the criteria published by Moreau et al.
- Serum creatinine ≥2 mg/dL (176.8 μmol/L).
- Serum bilirubin>5 mg/dL (85.5 μmol/L).
- 12. INR ≥2.5
- Bacterial infection within 10 days before study inclusion.
- Gastrointestinal bleeding within 10 days before study inclusion.
- Current overt hepatic encephalopathy, defined as grade II-IV hepatic encephalopathy according to the New-Haven classification.
- Patients with active hepatocellular carcinoma or history of hepatocellular carcinoma that is in remission for less than six months for uninodular HCC or for less than 12 months for multinodular HCC within Milan criteria.
- Patients on antiviral therapy for HCV or those who have received it within the last 6 months.
- Severe alcoholic hepatitis requiring corticosteroid therapy (Maddrey's Discriminant function ≥ 32 and/or ABIC score > 6.7).
- Patients with active alcohol consumption of more than 21 units per week.
- HIV infection.
- Patients with a history of significant extra hepatic disease with impaired short-term prognosis, including congestive heart failure New York Heart Association Grade III/IV, COPD GOLD >2, chronic kidney disease with serum creatinine >2mg/dL or under renal replacement therapy.
- Patients with current extra hepatic malignancies including solid tumours and hematologic disorders.
- Pregnancy or breastfeeding.
- Patients included in other clinical trials in the month before inclusion.
- Patients with mental incapacity, language barrier, bad social support or any other reason considered by the investigator precluding adequate understanding, cooperation or compliance in the study.
- Refusal to give informed consent.
Trial locations and contacts
14 sites in 7 countries.
14 sites in 7 countries
Spain6 sites
Hospital Clínic de Barcelona
Barcelona, España, 08036
Hospital Universitari Vall d'Hebrón
Barcelona, 08035
Hospital de Sant Pau
Barcelona
Hospital Moisés Broggi
Barcelona
Hospital Parc Taulí
Barcelona
Hospital Gregorio Marañón
Madrid
Italy3 sites
Bologna University Hospital
Bologna
Padova University Hospital
Padova, 35128
San Giovanni Battista Hospital
Torino, 10129
About this study
Official title: Efficacy of the Combination of Simvastatin Plus Rifaximin in Patients With Decompensated Cirrhosis to Prevent ACLF Development: a Multicenter, Double-blind, Placebo Controlled Randomized Clinical Trial
The aim of this study is to assess the efficacy of oral administration of simvastatin plus rifaximin in patients with decompensated cirrhosis to halt the progression of the disease as assessed by prevention of the development of ACLF
Read the detailed description
The current study was aimed at assessing whether a treatment based on combination of rifaximin and simvastatin would be effective in patients with decompensated cirrhosis to prevent ACLF development Considering that statins have been scarcely investigated in patients with decompensated cirrhosis due to a concern of potential higher liver and muscle toxicity in this population, a first LIVERHOPE_SAFETY clinical trial (unpublished) was undergone to assess safety and toxicity of statins with decompensated cirrhosis.
As a preliminary result of the LIVERHOPE_SAFETY clinical trial, it was concluded that the dose of Simvastatin 20mg per day plus Rifaximin is not associated to a higher risk of liver or muscle toxicity in patients with decompensated cirrhosis and simvastatin 20 mg was established for the LIVERHOPE_EFFICACY study.
- Conditions
- Liver Cirrhoses
- Being tested
- Simvastatin, Rifaximin, Placebo of Simvastatin, Placebo of Rifaximin
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SimvastatinDrug
Simvastatin 20 mg/day for 12 months
RifaximinDrug
Rifaximin 400/8 hours for 12 months
Placebo of SimvastatinDrug
Placebo of Simvastatin once a day for 12 months
Placebo of RifaximinDrug
Placebo of Rifaximin/8 hours for 12 months
| Study group | Role | What they receive |
|---|---|---|
| Simvastatin 20 mg + Rifaximin 400 mg | Experimental | Simvastatin 20 mg/day and rifaximin 400 mg/8 hours orally for 12 months Receives: Drug: Simvastatin; Drug: Rifaximin |
| Placebo of Simvastatin + Placebo of Rifaximin | Placebo comparator | Placebo of simvastatin and placebo of rifaximin orally for 12 months Receives: Drug: Placebo of Simvastatin; Drug: Placebo of Rifaximin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of ACLF at the end of the study
Measured: Month 12
Secondary outcomes (46)
Time to transplant-free survival at months1, 3, 6, 9 and 12
Measured: months 1, 3, 6, 9 and 12
Severity of ACLF assessed by number and types of organ failures at baseline, 1 month, 3 months, 6 months, 9 months and 12 months
Measured: months 1, 3, 6, 9 and 12
Frequency of hospital admissions due to complications of cirrhosis assessed at baseline, 1 month, 3 months, 6 months, 9 months and 12 months.
Measured: baseline and months 1, 3, 6, 9 and 12
Number of participants developing a new onset episode of ascitis assessed at baseline, 1 month, 3 months, 6 months, 9 months and 12 months
Measured: baseline and months 1, 3, 6, 9 and 12
Number of participants presenting worsening of ascitis assessed at baseline, 1 month, 3 months, 6 months, 9 months and 12 months
Worsening of ascitis will be defined as increased diuretic dosage or need for large-volume parecentesis in patients who had never been treated with this procedure
Measured: baseline and months 1, 3, 6, 9 and 12
Percentage of participants developing episodes of renal function impairment assessed at baseline, 1 month, 3 months, 6 months, 9 months and 12 months
Renal function impairment will be defined by AKI criteria, following criteria of the "EASL Clinical Practice Guidelines for the management of patients with decompensated cirrosis"
Measured: baseline and months 1, 3, 6, 9 and 12
Percentage of participants developing the first episode of bleeding by esophageal or gastric varices at baseline, 1 month, 3 months, 6 months, 9 months and 12 months
Measured: baseline and months 1, 3, 6, 9 and 12
Number of bleeding episodes by esophageal or gastric varices per patient assessed at baseline, 1 month, 3 months, 6 months, 9 months and 12 months
Measured: baseline and months 1, 3, 6, 9 and 12
Number of participants developing a new onset episode of hepatic encephalopathy (HE) assessed at baseline, 1 month, 3 months, 6 months, 9 months and 12 months
Measured: baseline and months 1, 3, 6, 9 and 12
Number of participants developing a new onset episode of bacterial infection assessed at baseline, 1 month, 3 months, 6 months, 9 months and 12 months
Measured: baseline and months 1, 3, 6, 9 and 12
Changes from baseline in plasma cytokine levels including, but not limited to, TNFα at 3 months, 6 months and 12 months
Measured: months 3, 6 and 12
Changes from baseline in plasma cytokine levels including, but not limited to, IL-6, IL-8, IL-10 and IL-1β at 3 months, 6 months and 12 months
Measured: months 3, 6 and 12
Changes from baseline in plasma cytokine levels including, but not limited to, IFN-ɣ at 3 months, 6 months and 12 months
Measured: months 3, 6 and 12
Changes from baseline in plasma cytokine levels including, but not limited to, G-CSF at 3 months, 6 months and 12 months
Measured: months 3, 6 and 12
Changes from baseline in plasma cytokine levels including, but not limited to, VCAM at 3 months, 6 months and 12 months
Measured: months 3, 6 and 12
Changes from baseline in plasma cytokine levels including, but not limited to, VCAM and VEGF at 3 months, 6 months and 12 months
Measured: months 3, 6 and 12
Changes from baseline in plasma cytokine levels including, but not limited to, oxide form of albumin at 3 months, 6 months and 12 months
Measured: months 3, 6 and 12
Changes from baseline in plasma cytokine levels including, but not limited to, HNA2 at 3 months, 6 months and 12 months
Measured: months 3, 6 and 12
Changes from baseline in plasma cytokine levels including, but not limited to, ADMA and SDMA at 3 months, 6 months and 12 months
Measured: months 3, 6 and 12
Changes from baseline in plasma biomarker FABP4 at 3 months, 6 months and 12 months
Measured: months 3, 6 and 12
Changes from baseline in plasma biomarker sCD-163 at 3 months, 6 months and 12 months
Measured: months 3, 6 and 12
Changes from baseline in plasma biomarker vWF at 3 months, 6 months and 12 months
Measured: months 3, 6 and 12
Changes from baseline in urine biomarker NGAL at 3 months, 6 months and 12 months
Measured: months 3, 6 and 12
Changes from baseline in urine biomarker MCP-1 at 3 months, 6 months and 12 months
Measured: months 3, 6 and 12
Changes from baseline in urine biomarker albumin at 3 months, 6 months and 12 months
Measured: months 3, 6 and 12
Changes from baseline in plasma renin concentration at 3 months, 6 months and 12 months
Measured: months 3, 6 and 12
Changes from baseline in plasma norepinephrine concentration at 3 months, 6 months and 12 months
Measured: months 3, 6 and 12
Changes from baseline in plasma copeptin concentration at 3 months, 6 months and 12 months
Measured: months 3, 6 and 12
Changes from baseline in blood levels of bacterial DNA or bacterial products at 3 months, 6 months and 12 months
Measured: months 3, 6 and 12
Changes in microbiome composition by analysis of microbial genes and signature at baseline, 3 months, 6 months and 12 months
The aim of this secondary endpoint is to identify phylogenetic and functional composition in the gut microbiota of patients at different stages of liver disease by analysis of microbial genes and signature.
As treatment with rifaximin has been associated to changes in microbiota composition in patients with cirrhosis, we will analyze the changes in microbiota signature and composition in patients under treatment with simvastatin and rifaximin at 3 months, 6 months and 12 months
Measured: baseline and months 3, 6 and 12
Changes from baseline in liver function evaluated by MELD (Model For End-Stage Liver Disease) score at 1 month, 3 months, 6 months, 9 months and 12 months
MELD score is a system developed to evaluate the severity of chronic liver disease, and it involves serum bilirubin, creatinine and international normalized ratio values
Measured: months 1, 3, 6, 9 and 12
Changes from baseline in liver function evaluated by CLIF-AD (Chronic Liver Failure - Acute Decompensation) score at 1 month, 3 months, 6 months, 9 months and 12 months
CLIF-AD score is a system created to evaluate the prognosis of patients with decompensated cirrosis, and it involves age, white cell count, creatinine, international normalized ratio and sodium
Measured: months 1, 3, 6, 9 and 12
Changes from baseline in liver function evaluated by Child Pugh Score at 1 month, 3 months, 6 months, 9 months and 12 months
Child Pugh is a score created to evaluate the prognosis of patients with cirrosis based on clinical and analytical values. It involves serum bilirubin, coagulation, albumin and the presence of clinical complications of cirrhosis, as hepatic encephalopathy and ascites
Measured: months 1, 3, 6, 9 and 12
Change in quality of life assessed by CLDQ questionnaire (Chronic Liver Disease Questionnaire) at baseline, 1 month, 3 months, 6 months, 9 months and 12 months
Evaluated by patient administration. CLDQ questionnaire contains 29 items divided into six domains: "Fatigue" which includes perceptions of decreased energy and sleepiness; "Emotional Function" which measures mood and insomnia; "Worry" assessing concerns regarding disease progression and family; "Activity" considering eating habits and movement of heavy objects; and finally, 2 symptom domains, "Abdominal Symptoms" and "Systemic Symptoms". All items refer to the previous 2 weeks on a 7 point Likert scale, with 1 corresponding to the maximum frequency ("all of the time") and 7 to the minimum ("none of the time"). Scores range from 1 (worst) to 7 (least severe), in which higher scores indicate a minimum frequency of symptoms and, consequently, a better quality of life
Measured: baseline and months 1, 3, 6, 9 and 12
Change of frailty and functional status assessed by Liver Frailty Index questionnaire at baseline, 1 month, 3 months, 6 months, 9 months and 12 months
Liver Frailty Index questionnaire is an objectively measure "physical frailty" (a term that we believe embodies these extrahepatic manifestations of cirrhosis) in patients with end-stage liver disease (ESLD) and quantify its impact on health-related outcomes. It's composed by (1) Gender (Male or Female); (2) Dominant hand grip strength (kg), the means of three measures; (3) Chair stands (sec), time that it takes a patient to stand up and sit down in a chair 5 times without using their arms; and (4) Balance (sec), seconds holding 3 position balance tested in 3 positions for 10 seconds each the positions are side by side, semi tandem and tandem.
Liver Frailty Index is calculated as: (-0:330 * gender-adjusted grip strength) + (-2:529 * number of chair stands per second) + (-0:040 * balance time) + 6.
The questionnaire does not have a minimum value and a maximum value.
Measured: baseline and months 1, 3, 6, 9 and 12
Change of minimal hepatic encephalopathy assessed by PHES questionnaire (Psychometric Hepatic Encephalopathy Score) at baseline, 1 month, 3 months, 6 months, 9 months and 12 months
The PHES is a questionnaire used in the diagnosis of minimal hepatic encephalopathy (MHE) and can be used to assess motor speed, motor accuracy, concentration, attention, visual perception, visual-spatial orientation, visual construction and memory, which are related to most of neuropsychological impairments in MHE. The PHES is composed of five tests, number connection test-A (NCT-A), number connection test-B (NCT-B), serial dotting test (SDT), line tracing test (LTT) and digit symbol test (DST). This questionnaire measures the time that the patient spends doing the five exercises.
The questionnaire does not have a minimum value and a maximum value, but as the score increases there is a worsening of outcome.
Measured: baseline and months 1, 3, 6, 9 and 12
Changes from baseline in stigmatization assessed by a specific questionnaire at 3 months, 6 months and 12 months
Evaluated by patient administration. This questionnaire quantifies the presence of stigma among patients with cirrhosis. The questionnaire gives a total of 19 stigma-related questions with answer choices based on a four point Likert scale (strongly agree, agree, disagree, and strongly disagree). The questions are divided in four categories 1) discrimination, 2) stereotypes, 3) social isolation and 4) shame. The questionnaire does not have a minimum value and a maximum value, because is only a descriptive questionnaire that values patient perception regarding the disease.
Measured: months 3, 6 and 9
Change in appearance of muscle toxicity at baseline, 1 month, 3 months, 6 months, 9 months and 12 months as defined using a specific statin-associated myopathy questionnaire
Appearance of muscle toxicity at baseline, 1 month, 3 months, 6 months, 9 months and 12 months as defined using a specific statin-associated myopathy questionnaire. This questionnaire consists of four questions that patients can answer yes or no. The patients met the study definition for "appearance of muscle toxicity" if one of the three of the following occurred: 1) They reported new or increased muscle pain, cramps, or aching, unassociated with exercise; 2) Symptoms persisted for at least 2 weeks; 3) Symptoms resolved within 2 weeks of stopping the study drug; and 4) Symptoms reoccurred within 4 weeks of restarting the study medication.
Measured: baseline and months 1, 3, 6, 9 and 12
Number of patients with genetic polymorphisms of statins membrane transporter OATPB1 in all patients included in the study
Measured: month 12
Changes from baseline in transaminases at 1 month, 3 months, 6 months, 9 months ans 12 months
Measured: months 1, 3, 6, 9 and 12
Changes from baseline in alkaline phosphatase at 1 month, 3 months, 6 months, 9 months ans 12 months
Measured: months 1, 3, 6, 9 and 12
Changes from baseline in creatine kinase at 1 month, 3 months, 6 months, 9 months ans 12 months
Measured: months 1, 3, 6, 9 and 12
Proportion of patients and severity of treatment-related adverse events during the study period
Measured: month 12
Annualized incidence of ACLF during the study period
Measured: month 12
Time to overall at the end of the study
Measured: month 12
Time to disease related survival at the end of the study
Measured: month 12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Dec 2018
- Study start3 Jan 2019
- Primary completion1 Dec 2022
- Study completion1 Dec 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Liver CirrhosesStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Phase III, multicentre, double-blind placebo-controlled, randomized clinical trial
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 254 participants (actual)
Sponsor and investigators
- Lead sponsor
- Judit Pich
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Judit Pich, Institut d'Investigacions Biomèdiques August Pi i Sunyer
- Investigators
- Pere Ginès, MD, Study chair, Hospital Clinic of Barcelona
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03780673
- Sponsor's protocol ID
- LIVERHOPE_EFFICACY
- Acronym
- 2018-001698-25
- Status last verified
- May 2023
- First submitted
- 29 Nov 2018
- Last updated
- 24 May 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Pose E, Jimenez C, Zaccherini G, Campion D, Piano S, Uschner FE, de Wit K, Roux O, Gananandan K, Laleman W, Sole C, Alonso S, Cuyas B, Ariza X, Juanola A, Ma AT, Napoleone L, Gratacos-Gines J, Tonon M, Pompili E, Sanchez-Delgado J, Allegretti AS, Morales-Ruiz M, Carol M, Perez-Guasch M, Fabrellas N, Pich J, Martell C, Joyera M, Domenech G, Rios J, Torres F, Serra-Burriel M, Hernaez R, Sola E, Graupera I, Watson H, Soriano G, Banares R, Mookerjee RP, Francoz C, Beuers U, Trebicka J, Angeli P, Alessandria C, Caraceni P, Vargas VM, Abraldes JG, Kamath PS, Gines P; LIVERHOPE Consortium. Simvastatin and Rifaximin in Decompensated Cirrhosis: A Randomized Clinical Trial. JAMA. 2025 Mar 11;333(10):864-874. doi: 10.1001/jama.2024.27441.
PubMed 39908052Marrache MK, Rockey DC. Statins for treatment of chronic liver disease. Curr Opin Gastroenterol. 2021 May 1;37(3):200-207. doi: 10.1097/MOG.0000000000000716.
PubMed 33654016
Study at a glance
From the registry record, last updated by the sponsor on 24 May 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy of the Combination of Simvastatin Plus Rifaximin in Patients With Decompensated Cirrhosis to Prevent ACLF Development: a Multicenter, Double-blind, Placebo Controlled Randomized Clinical Trial
- ClinicalTrials.gov ID
- NCT03780673
- Acronym / sponsor ID
- 2018-001698-25 / LIVERHOPE_EFFICACY
- Conditions
- Liver Cirrhoses
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 254 participants (actual)
- Lead sponsor
- Judit PichUniversity, hospital or other
- Study start
- 3 Jan 2019 (actual)
- Primary completion
- 1 Dec 2022 (actual)
- Study completion
- 1 Dec 2022 (actual)
- First posted
- 19 Dec 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The aim of this study is to assess the efficacy of oral administration of simvastatin plus rifaximin in patients with decompensated cirrhosis to halt the progression of the disease as assessed by prevention of the development of ACLF
Detailed description
The current study was aimed at assessing whether a treatment based on combination of rifaximin and simvastatin would be effective in patients with decompensated cirrhosis to prevent ACLF development Considering that statins have been scarcely investigated in patients with decompensated cirrhosis due to a concern of potential higher liver and muscle toxicity in this population, a first LIVERHOPE_SAFETY clinical trial (unpublished) was undergone to assess safety and toxicity of statins with decompensated cirrhosis.
As a preliminary result of the LIVERHOPE_SAFETY clinical trial, it was concluded that the dose of Simvastatin 20mg per day plus Rifaximin is not associated to a higher risk of liver or muscle toxicity in patients with decompensated cirrhosis and simvastatin 20 mg was established for the LIVERHOPE_EFFICACY study.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
- Model description
- Phase III, multicentre, double-blind placebo-controlled, randomized clinical trial
| Arm | Type | Receives |
|---|---|---|
| Simvastatin 20 mg + Rifaximin 400 mg | Experimental | Drug: Simvastatin, Drug: RifaximinSimvastatin 20 mg/day and rifaximin 400 mg/8 hours orally for 12 months |
| Placebo of Simvastatin + Placebo of Rifaximin | Placebo comparator | Drug: Placebo of Simvastatin, Drug: Placebo of RifaximinPlacebo of simvastatin and placebo of rifaximin orally for 12 months |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Age ≥ 18 years old
- Cirrhosis defined by standard clinical criteria, ultrasonographic findings and/or histology
- Child-Pugh patients or Child-Pugh C patients (up to 12 points)
- Women of child-bearing potential must have a negative pregnancy test in serum before the inclusion in the study and agree to use highly effective contraceptive methods during the study. Highly effective contraceptive methods will include: intrauterine device, bilateral tubal occlusion, vasectomized partner and sexual abstinence.
Key exclusion criteria (26 listed)
- Patients on treatment with statins or rifaximin up to one month before study inclusion.
- Patients with contraindications for statins or rifaximin therapy.
- Known hypersensitivity to simvastatin or rifaximin (or rifamycin derivatives).
- Patients with CK elevation of 50% or more above the upper limit of normal at study inclusion.
- Patients on treatment with potent inhibitors of CYP3A4 enzyme
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SimvastatinSimvastatin 20 mg/day for 12 months | Drug | Simvastatin 20 mg + Rifaximin 400 mg |
| RifaximinRifaximin 400/8 hours for 12 months | Drug | Simvastatin 20 mg + Rifaximin 400 mg |
| Placebo of SimvastatinPlacebo of Simvastatin once a day for 12 months | Drug | Placebo of Simvastatin + Placebo of Rifaximin |
| Placebo of RifaximinPlacebo of Rifaximin/8 hours for 12 months | Drug | Placebo of Simvastatin + Placebo of Rifaximin |
Primary outcome
Incidence of ACLF at the end of the study
Time frame: Month 12
46 secondary outcomes
Time to transplant-free survival at months1, 3, 6, 9 and 12
Time frame: months 1, 3, 6, 9 and 12
Severity of ACLF assessed by number and types of organ failures at baseline, 1 month, 3 months, 6 months, 9 months and 12 months
Time frame: months 1, 3, 6, 9 and 12
Frequency of hospital admissions due to complications of cirrhosis assessed at baseline, 1 month, 3 months, 6 months, 9 months and 12 months.
Time frame: baseline and months 1, 3, 6, 9 and 12
Number of participants developing a new onset episode of ascitis assessed at baseline, 1 month, 3 months, 6 months, 9 months and 12 months
Time frame: baseline and months 1, 3, 6, 9 and 12
Number of participants presenting worsening of ascitis assessed at baseline, 1 month, 3 months, 6 months, 9 months and 12 months
Time frame: baseline and months 1, 3, 6, 9 and 12
Percentage of participants developing episodes of renal function impairment assessed at baseline, 1 month, 3 months, 6 months, 9 months and 12 months
Time frame: baseline and months 1, 3, 6, 9 and 12
Percentage of participants developing the first episode of bleeding by esophageal or gastric varices at baseline, 1 month, 3 months, 6 months, 9 months and 12 months
Time frame: baseline and months 1, 3, 6, 9 and 12
Number of bleeding episodes by esophageal or gastric varices per patient assessed at baseline, 1 month, 3 months, 6 months, 9 months and 12 months
Time frame: baseline and months 1, 3, 6, 9 and 12
Number of participants developing a new onset episode of hepatic encephalopathy (HE) assessed at baseline, 1 month, 3 months, 6 months, 9 months and 12 months
Time frame: baseline and months 1, 3, 6, 9 and 12
Number of participants developing a new onset episode of bacterial infection assessed at baseline, 1 month, 3 months, 6 months, 9 months and 12 months
Time frame: baseline and months 1, 3, 6, 9 and 12
Changes from baseline in plasma cytokine levels including, but not limited to, TNFα at 3 months, 6 months and 12 months
Time frame: months 3, 6 and 12
Changes from baseline in plasma cytokine levels including, but not limited to, IL-6, IL-8, IL-10 and IL-1β at 3 months, 6 months and 12 months
Time frame: months 3, 6 and 12
Changes from baseline in plasma cytokine levels including, but not limited to, IFN-ɣ at 3 months, 6 months and 12 months
Time frame: months 3, 6 and 12
Changes from baseline in plasma cytokine levels including, but not limited to, G-CSF at 3 months, 6 months and 12 months
Time frame: months 3, 6 and 12
Changes from baseline in plasma cytokine levels including, but not limited to, VCAM at 3 months, 6 months and 12 months
Time frame: months 3, 6 and 12
Changes from baseline in plasma cytokine levels including, but not limited to, VCAM and VEGF at 3 months, 6 months and 12 months
Time frame: months 3, 6 and 12
Changes from baseline in plasma cytokine levels including, but not limited to, oxide form of albumin at 3 months, 6 months and 12 months
Time frame: months 3, 6 and 12
Changes from baseline in plasma cytokine levels including, but not limited to, HNA2 at 3 months, 6 months and 12 months
Time frame: months 3, 6 and 12
Changes from baseline in plasma cytokine levels including, but not limited to, ADMA and SDMA at 3 months, 6 months and 12 months
Time frame: months 3, 6 and 12
Changes from baseline in plasma biomarker FABP4 at 3 months, 6 months and 12 months
Time frame: months 3, 6 and 12
Changes from baseline in plasma biomarker sCD-163 at 3 months, 6 months and 12 months
Time frame: months 3, 6 and 12
Changes from baseline in plasma biomarker vWF at 3 months, 6 months and 12 months
Time frame: months 3, 6 and 12
Changes from baseline in urine biomarker NGAL at 3 months, 6 months and 12 months
Time frame: months 3, 6 and 12
Changes from baseline in urine biomarker MCP-1 at 3 months, 6 months and 12 months
Time frame: months 3, 6 and 12
Changes from baseline in urine biomarker albumin at 3 months, 6 months and 12 months
Time frame: months 3, 6 and 12
Changes from baseline in plasma renin concentration at 3 months, 6 months and 12 months
Time frame: months 3, 6 and 12
Changes from baseline in plasma norepinephrine concentration at 3 months, 6 months and 12 months
Time frame: months 3, 6 and 12
Changes from baseline in plasma copeptin concentration at 3 months, 6 months and 12 months
Time frame: months 3, 6 and 12
Changes from baseline in blood levels of bacterial DNA or bacterial products at 3 months, 6 months and 12 months
Time frame: months 3, 6 and 12
Changes in microbiome composition by analysis of microbial genes and signature at baseline, 3 months, 6 months and 12 months
Time frame: baseline and months 3, 6 and 12
Changes from baseline in liver function evaluated by MELD (Model For End-Stage Liver Disease) score at 1 month, 3 months, 6 months, 9 months and 12 months
Time frame: months 1, 3, 6, 9 and 12
Changes from baseline in liver function evaluated by CLIF-AD (Chronic Liver Failure - Acute Decompensation) score at 1 month, 3 months, 6 months, 9 months and 12 months
Time frame: months 1, 3, 6, 9 and 12
Changes from baseline in liver function evaluated by Child Pugh Score at 1 month, 3 months, 6 months, 9 months and 12 months
Time frame: months 1, 3, 6, 9 and 12
Change in quality of life assessed by CLDQ questionnaire (Chronic Liver Disease Questionnaire) at baseline, 1 month, 3 months, 6 months, 9 months and 12 months
Time frame: baseline and months 1, 3, 6, 9 and 12
Change of frailty and functional status assessed by Liver Frailty Index questionnaire at baseline, 1 month, 3 months, 6 months, 9 months and 12 months
Time frame: baseline and months 1, 3, 6, 9 and 12
Change of minimal hepatic encephalopathy assessed by PHES questionnaire (Psychometric Hepatic Encephalopathy Score) at baseline, 1 month, 3 months, 6 months, 9 months and 12 months
Time frame: baseline and months 1, 3, 6, 9 and 12
Changes from baseline in stigmatization assessed by a specific questionnaire at 3 months, 6 months and 12 months
Time frame: months 3, 6 and 9
Change in appearance of muscle toxicity at baseline, 1 month, 3 months, 6 months, 9 months and 12 months as defined using a specific statin-associated myopathy questionnaire
Time frame: baseline and months 1, 3, 6, 9 and 12
Number of patients with genetic polymorphisms of statins membrane transporter OATPB1 in all patients included in the study
Time frame: month 12
Changes from baseline in transaminases at 1 month, 3 months, 6 months, 9 months ans 12 months
Time frame: months 1, 3, 6, 9 and 12
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 May 2023.
- Derived from this study: PubMed 39908052Pose E, Jimenez C, Zaccherini G, Campion D, Piano S, Uschner FE, de Wit K, Roux O, Gananandan K, Laleman W, Sole C, Alonso S, Cuyas B, Ariza X, Juanola A, Ma AT, Napoleone L, Gratacos-Gines J, Tonon M, Pompili E, Sanchez-Delgado J, Allegretti AS, Morales-Ruiz M, Carol M, Perez-Guasch M, Fabrellas N, Pich J, Martell C, Joyera M, Domenech G, Rios J, Torres F, Serra-Burriel M, Hernaez R, Sola E, Graupera I, Watson H, Soriano G, Banares R, Mookerjee RP, Francoz C, Beuers U, Trebicka J, Angeli P, Alessandria C, Caraceni P, Vargas VM, Abraldes JG, Kamath PS, Gines P; LIVERHOPE Consortium. Simvastatin and Rifaximin in Decompensated Cirrhosis: A Randomized Clinical Trial. JAMA. 2025 Mar 11;333(10):864-874. doi: 10.1001/jama.2024.27441.
- Derived from this study: PubMed 33654016Marrache MK, Rockey DC. Statins for treatment of chronic liver disease. Curr Opin Gastroenterol. 2021 May 1;37(3):200-207. doi: 10.1097/MOG.0000000000000716.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Pere Ginès, MD study chair
Hospital Clinic of Barcelona
14 sites in 7 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Simvastatin and Rifaximin in people with Liver Cirrhoses, run by Judit Pich at 14 sites in 7 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 26 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 24 May 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 14 sites in Spain, Italy, Belgium, France, Germany and 2 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of ACLF at the end of the study (time frame: Month 12). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03780673, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 May 2023.